Table 2 List of genes with significant editing dysregulation, namely, observed differential editing in exonic regions with effects on protein-coding regions, in neurologically or immune relevant pathways, or in multiple samples. Parenthetical numbers next to a dataset for a given gene specify that > 1 site was differentially edited in that gene/dataset
From: Changes in ADAR RNA editing patterns in CMV and ZIKV congenital infections
Gene | Dataset(s) | Genic location of edited site/Effect | Function/significance of edited gene |
|---|---|---|---|
Neurological: | Â | Â | |
 Gria3 | PRJNA358758 | Exon (nonsyn) | AMPA glutamate receptor subunit, editing allows faster recovery from desensitization [76] |
 Grik5 | PRJNA358758 | Exon (nonsyn) | Kainate glutamate receptor subunit associated with psychiatric, eye, and vascular diseases [77, 78] |
 Calm1 | PRJNA358758, PRJNA487357 | 3′ UTR | Ca2 + −binding messenger impacting numerous neurological functions [81, 114, 115] |
 Camk4 | PRJNA358758 | 3′ UTR | Signal transducer downstream of Calmodulin with important and diverse neurological and immune functions [116] |
 Map6 | PRJNA358758 | 3′ UTR | Calmodulin binding protein regulating microtubule stability, important for proper axon development, disruption leads to issues with neurotransmission and synapse formation, as well as cognitive/behavioral deficits [87,88,89,90,91,92,93,94] |
 Selenot | PRJNA358758 (2), PRJNA487357 | 3′ UTR | Thioredoxin-like oxidoreductase, neuroprotective, highly expressed during brain development, KO affects brain structure through neuron loss and causes behavioral changes, important role in brain development [117] |
 Sgpl1 | PRJNA358758, PRJEB38849 | 3′ UTR | Sphingosine phosphate lyase, regulates neuronal autophagy [118], microglial autophagy and inflammation [119], mutations linked with neurological pathologies [120,121,122] |
 Arhgdia | PRJNA358758, PRJEB38849 (2) | 3′ UTR | Regulator of Rho GTPase signaling, regulates cell proliferation and migration, underexpression promotes glioma progression [123, 124]; Rho GTPase signaling plays an important role in neurodevelopment and dysregulation may lead to neurological disorders [125] |
 NCK2 | PRJNA551246 | Intron | Tyrosine kinase adaptor protein regulating cytoskeleton organization and formation of neuronal connections [105,106,107] |
Immune: | Â | Â | Â |
 Lgals3 | PRJNA358758 | Exon (nonsyn) | Galectin with affinity for beta-galactosides, can regulate adhesion/inflammation of immune cells, can affect cell growth/differentiation, including immune cell/neurite growth, and acts as a splicing factor along with other functions [126,127,128] |
 Tapbp | PRJNA358758 (3), PRJNA487357 (2), PRJEB38849 (2) | 3′ UTR | Mediates interaction between MHC1 and TAP to allow loading of antigenic peptides [129] |
 Xbp1 | PRJNA358758, PRJEB38849 | 3′ UTR | Transcription factor regulating immune and UPR functions, also with links to neurodegenerative disease [130] |
 Ube2d3 | PRJNA358758 | 3′ UTR | E2 ubiquitin ligase, involved in RIG-1 activation [131] |
 RIG1 | PRJNA551246 (3) | 3′ UTR | dsRNA sensor responsible for activating innate antiviral type 1 interferon response [132] |
 IFITM2 | PRJNA551246 | Exon (nonsyn) | |
Other: | Â | Â | Â |
 Ucp2 | PRJNA358758 | Exon (nonsyn) | Mitochondrial uncoupling protein (proton leak), attenuates mitochondrial ROS production. Reduced expression is linked to altered differentiation of NPCs and has a significant role in brain development [133, 134] |
 Ogdh | PRJNA358758 | Exon (stoploss) | 2-oxoglutarate dehydrogenase complex subunit, some evidence of links to neurological disease [135, 136] |
 Azin1 | PRJNA358758 | Exon (nonsyn) | Antizyme inhibitor regulating intracellular polyamine levels, ADAR editing of this gene is linked to development of a number of cancers, including colorectal, non-small-cell lung, gastric, and hepatocellular cancers [137,138,139,140,141,142], as well as to hematopoietic stem cell differentiation [143] |
 Nova1 | PRJNA358758 | Exon (nonsyn) | RBP regulating splicing and degradation of a number of genes with important neurological functions through brain development: editing is dynamically regulated during development and increases protein stability [97,98,99] |
 Celf1 | PRJNA358758 | 3′ UTR | RBP regulating splicing during brain development [144] |
 Sf3b2 | PRJNA358758, PRJNA487357, PRJEB38849 | 3′ UTR | Splicing factor, U2 snRNP component, variants associated with craniofacial microsomia [145] |
 Sept2 | PRJNA358758, PRJNA487357, PRJEB38849 | 3′ UTR | Cytoskeletal GTP-binding filament-forming protein Sept2 [146] is expressed in the brain, and neurological functions include regulation of astrocyte glutamate uptake [147] |
 Lamp2 | PRJNA358758 (3), PRJEB38849 (3) | 3′ UTR | Lysosome membrane glycoprotein, dysregulation of RNA editing by APOBEC1 in this gene in mouse microglia causes neurological dysfunction and neurodegeneration [95, 148] |
 Phc2 | PRJNA358758, PRJNA487357 | 3′ UTR | Component of class II PcG complex and PRC1, contributes to epigenetic regulation of gene expression, including neurogenic genes during brain development [101,102,103,104] |
 H19 | PRJNA358758, PRJNA487357 | lncRNA | lncRNA which functions as a tumor suppressor and regulates growth during embryonic development [149, 150] |
 Gpx3 | PRJNA358758, PRJEB38849 | 3′ UTR | Glutathione peroxidase, reduces hydrogen peroxide to prevent oxidative damage [151] |
 Fam49b (a.k.a. Cyrib) | PRJNA358758, PRJEB38849 | Exon (syn) | Interacts with Rac GTPase, functions include mitochondrial ROS suppression, modulating cytoskeleton organization, and inhibition of T cell activation [152, 153] |
 Tmem50b | PRJNA358758, PRJEB38849 | 3′ UTR | Transmembrane protein, ER localization, may contribute to proper brain development, with dysregulation leading to Down syndrome-related phenotypes [154] |
 Cap1 | PRJNA358758 | 3′ UTR | Regulates cytoskeleton organization, adhesion, cAMP signaling [155]. Also plays a role in regulating neuron differentiation [156, 157] |